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The cardiac renin-angiotensin-aldosterone system and hypertensive cardiac hypertrophy
V K Raman1, Y A Lee, K Lindpaintner
1Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Insights
The cardiac renin-angiotensin system plays a direct role in cardiac hypertrophy. Understanding this local system offers new therapeutic targets for heart conditions.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
Background:
- Systemic hypertension-induced ventricular hypertrophy suggests a role for the renin-angiotensin system.
- Angiotensin II exhibits direct trophic effects on the heart in experimental models.
Purpose of the Study:
- To explore the direct involvement of the cardiac renin-angiotensin system in cardiac hypertrophy.
- To investigate the local intracardiac renin-angiotensin system's components and functions.
Main Methods:
- Review of experimental systems demonstrating angiotensin II trophic effects.
- Evidence synthesis for the existence and function of an intracardiac renin-angiotensin system.
- Analysis of studies on local system modulation and differential expression in pathological conditions.
Main Results:
- Conclusive evidence supports a local cardiac renin-angiotensin system capable of synthesizing all components.
- The local system can cleave angiotensin peptides from angiotensinogen via the classic pathway.
- The cardiac renin-angiotensin system's activity is modulated by pharmacologic agents and differentially expressed in hypertrophy and post-myocardial infarction remodeling.
Conclusions:
- The cardiac renin-angiotensin system is implicated in the pathogenesis of cardiac hypertrophy.
- Further research into this local system can lead to targeted therapeutic strategies for cardiac hypertrophy and failure.
Abstract:
Angiotensin-converting enzyme inhibitors have proven to be uniquely effective in inducing regression, or preventing the occurrence, of ventricular hypertrophy associated with systemic hypertension. This has pointed, for many years, to a possible direct involvement of the renin-angiotensin system in the pathogenesis of cardiac hypertrophy. Over the last 10 years further supporting evidence has been forthcoming about direct trophic effects of angiotensin II in several experimental systems. Additionally, we now have rather conclusive evidence for the existence of a local, intracardiac renin-angiotensin system, which is capable of synthesis of all components of the system, and of cleaving, via the classic pathway, angiotensin peptides from the precursor, angiotensinogen. Moreover, a number of studies have demonstrated the capacity of regulatory response and modulation of activity of the local system in response to a variety of pharmacologic perturbations as well as differential expression of specific components under pathologic conditions, including compensatory hypertrophy and remodeling after myocardial infarction, pressure overload hypertrophy, and volume overload hypertrophy. Continued research into the role of the cardiac renin-angiotensin system in the pathogenesis of cardiac hypertrophy and failure will provide us with the tools to devise more specific, targeted strategies for therapeutic intervention or prevention.